糖络宁对糖尿病周围神经病变大鼠细胞凋亡相关通路的影响

Influence of Tangluoning on apoptosis related pathway in diabetic peripheral neuropathy rats

目的观察糖络宁对糖尿病周围神经病变(DPN)大鼠坐骨神经组织中PI3K/AKT及PERK信号传递通路的调节作用。方法选用8周龄的清洁级雄性SD大鼠80只,随机选择14只为正常组,其余66只通过一次性腹腔内注射链脲佐菌素60 mg/kg,诱导大鼠高血糖,建造DPN大鼠实验模型。将造模成功的61只大鼠采用随机数字表法分为模型对照组(模型组,21只)、糖络宁组(中药组,21只)、α-硫辛酸治疗组(西药组,19只)。中药组予糖络宁5 g/(kg·d)一次灌胃,西药组予α-硫辛酸20 mg/(kg·d)一次灌胃,模型组每天予等量蒸馏水灌胃,各组均连续用药8周。8周后通过Western blot检测坐骨神经中p-PI3K、p-pPI3K、p-AKT、p-pAKT、p-PERK、p-pPERK蛋白的表达。结果各组大鼠脊髓背根神经节(DRG)中p-PI3K、p-pPI3K、p-AKT、p-pAKT、p-PERK、p-pPERK蛋白表达比较,差异均有统计学意义(P<0.05)。与正常组比较,模型组大鼠DRG中p-PI3K、p-pPI3K、p-AKT、p-pAKT蛋白表达显著降低(P<0.01),p-PERK、p-pPERK蛋白表达显著升高(P<0.01);与模型组比较,中药组、西药组大鼠DRG中p-PI3K、p-pPI3K、p-AKT、p-pAKT蛋白表达升高(P<0.05),p-PERK、p-pPERK蛋白表达降低(P<0.05)。结论糖络宁可通过激活PI3K/AKT和信号传递通路,抑制PERK信号传递通路,改善神经细胞凋亡状况,抑制神经损伤。

Objective To observe the regulatory effect of Tangluoning on PI3K/AKT and PERK signaling pathway in sciatic nerve tissue of diabetic peripheral neuropathy(DPN)rats.Methods Eighty eight-week-old male SD rats of clean grade were selected.Fourteen rats were randomly selected as normal group.The other 66 rats were induced hyperglycemia by intraperitoneal injection of streptozotocin 60 mg/kg.Sixty-one rats were randomly divided into model control group(model group,21 rats),Tangluoning group(traditional Chinese medicine group,21 rats),α-lipoic acid treatment group(Western medicine group,19 rats).Traditional Chinese medicine group was given Tangluoning 5 g/(kg·d),Western medicine group was givenα-lipoic acid 20 mg/(kg·d)once a day.Model group was given the same amount of distilled water by gavage every day.All groups were treated for eight weeks.After eight weeks,the expression of p-PI3K,p-pPI3K,p-AKT,p-pAKT,p-PERK and p-pPERK protein in sciatic nerve was detected by Western blot.Results The expression of p-PI3K,p-pPI3K,p-AKT,p-pAKT,p-PERK and p-pPERK protein in dorsal root ganglion(DRG)of rats in each group had statistical significance(P<0.05).Compared with normal group,the protein expressions of p-PI3K,p-pPI3K,p-AKT and p-pAKT in DRG of model group were significantly decreased(P<0.01),and the protein expressions of p-PERK and p-pPERK were significantly increased(P<0.01).Compared with model group,the protein expressions of p-PI3K,p-pPI3K,p-AKT and p-pAKT in the DRG of Chinese medicine group and Western medicine group were increased(P<0.05),and the protein expressions of p-PERK and p-pPERK were decreased(P<0.05).Conclusion Tangluoning can regulate PI3K/AKT and PERK signaling pathway so as to inhibiting apoptosis and avoid nerve injury.